Currently, the only FDA approved treatment for acute stroke is intravenous tissue plasminogen activator (iv tPA) administered within three hours after symptom onset. Only three percent of stroke patients in the United States receive iv tPA, because most patients present to the hospital beyond the three hour time-limit for iv tPA. Although clinical trials have not demonstrated benefit from iv tPA beyond three hours, a subgroup of stroke patients who benefit is likely to exist. This subgroup needs to be identified in order to increase the proportion of stroke patients who may be treated with tPA. The candidate proposes, in three Specific Aims, to investigate whether 1) clinical, 2) computed tomography (CT) and 3) magnetic resonance imaging (MRI) characteristics help identify patients who are most likely to have a favorable response to iv tPA in the three to six hour time-window. Based on the results of these projects, the candidate intents to develop a practical clinical prediction tool, which will enable physicians to stratify acute stroke patients and identify those who are most likely to have a favorable response to tPA. Dr. Lansberg is completing his Cerebrovascular Fellowship at Stanford University Medical Center and he will join the staff of the Department of Neurology and Neurological Sciences at Stanford University on July 1, 2004. His career goal is to improve the health of stroke patients through clinical research and direct patient care. His career development plan combines a highly relevant clinical research proposal with complementary didactic training. He will complete a Master of Science Program in Clinical Epidemiology and Biostatistics and he will get training in MRI technology. The candidate has a team of mentors who are world-renowned researchers in the following four fields: Clinical studies of acute stroke, neuroradiology, MRI physics and biostatistics. They will provide guidance throughout the award period and facilitate his transition into a successful independent investigator. [unreadable] [unreadable]